Airway epithelial cells can produce and secret both antibacterial enzymes and amphipathic (hydrophilic–positively charged) antimicrobial peptides, which generally target and disrupt cell wall components of the bacteria, which leads to cell death. Lysozyme, elastase, hydrolases, and secretory phospholipase A2 are examples of antibacterial enzymes targeted at various pathogens. Antimicrobial peptides are typically cationic peptides synthesized as propeptides and activated through cleavage of an anionic propiece. Peptides secreted from epithelial cells and alveolar macrophages usually enter the mucosal fluid, whereas peptides secreted from submucosal macrophages typically stay within the local tissue.
There are three classes of antimicrobial peptides: defensins, cathelicidins, and histatins. Defensins, which are categorized as α and β can disrupt cell membranes within minutes and are very effective on bacteria, fungi, and viruses. β–Defensins are synthesized in alveolar type II cells, are stored in lamellar bodies, and are a component of surfactant. α–Defensins are synthesized and stored within epithelial cells, macrophages, and neutrophils. Cathelicidins are stored in secondary granules and activated intracellularly by fusion of the phagosomes with the granule or also directly by elastase. In the lungs, cathelicidins are secreted from lung type II epithelial cells, as well as from neutrophils and macrophages. Histatins are present mainly in the oral cavity and are more specific for pathogenic fungi. Although it is not clear whether they exist in the respiratory tract, the carbodydrate-binding proteins (lectins) in the gut can directly kill Gram-positive bacteria by binding to their cell walls. Furthermore, lactoferrins and lysozyme present in epithelial cells have been shown to have bacteriostatic and bactericidal effects; the precise mechanism by which this occurs is not clearly understood, although it is postulated that they may work synergistically with iron and calcium.
The human microbiome, especially the gut, has received a lot of attention, and exploration into the role of these commensal microorganisms in health and disease is rapidly developing. Although much is known about the gut microbiome, the lung microbiome has been difficult to explore. Once thought to be a sterile environment, the lung remains a difficult site to sample for a variety of reasons, including subject safety during sampling (invasive procedures), complexity and variety of epithelial surfaces throughout the respiratory tract, and the simple fact that far fewer bacteria are available to sample. Furthermore, the lumen ecosystem and epithelium of the respiratory tract differ considerably along the respiratory tract, from the upper airways to the alveoli; it is likely that the density and types of bacteria residing in these various regions also differ. It is clear, however, that the lung does have a microbiome, and three primary phyla appear to be represented: Bacteroidetes (Prevotella, Bacteroides), Firmicutes (Veillonella, Streptococcus, Staphylococcus), and Proteobacteria (Pseudomonas, Haemophilus, Moraxella, Neisseria, Acinetobacter).